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| Disease | Genetic background | Disease related phenotype | Affected neurons | iPSCs model | References |
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| Neurodegenerative disorders |
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| Alzheimer’s disease | PS1, PS2, APP duplication, ApoE | (i) Increased Aβ42 secretion;
(ii) Aβ plaque formation;
(iii) increased phospho-Tau;
(iv) increased GSK3β activity | Basal forebrain cholinergic neurons; cortical neurons | (i) AD iPSCs with E693 deletion in APP gene;
(ii) AD iPSCs with mutation in APP (V717I);
(iii) AD iPSCs with a duplication APP gene;
(iv) AD iPSCs with PS1 (A246E) and PS2 (N141I) mutation | [40–43] |
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| Parkinson’s disease | SNCA, LRRK2, PARKN, PINK1, UCHL1, GBA | (i) α-Synuclein accumulation;
(ii) reduced numbers of neuritis;
(iii) increased susceptibility to oxidative stress;
(iv) accumulation of ER-associated degradation substrates | Dopaminergic neurons | (i) PD iPSCs with triplication of the SNCA;
(ii) PD iPSCs with α-synuclein mutation (A53T);
(iii) PD iPSCs with G2019S mutation in LRRK2 gene;
(iv) PD iPSCs with mutation in PINK1 | [53, 54, 57, 63] |
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| SMA | SMN1, SMN2 | (i) Reduced SMN gene expression;
(ii) Fas ligand-mediated apoptosis of MN;
(iii) increased level of caspase 3, caspase 8, and membrane-bound Fas ligand;
(iv) reduced size, axonal elongation, and neuromuscular junction production | Motor neurons | (i) iPSCs with SMN1 mutation from SMA type I patients | [64, 65] |
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| ALS | SOD1, TDP-43, FUS, VAPB | (i) Neurofilament-L aggregation in neuritis;
(ii) axonal degeneration;
(iii) increased secretion of TDP-43;
(iv) exhibited shortened neurites | Motor neurons | (i) ALS iPSCs with A4V SOD1 mutation;
(ii) ALS iPSCs with D90A SOD1 mutation;
(iii) ALS iPSCs with mutation invTDP-43 gene;
(iv) ALS iPSCs with VAPB (P56S) mutation | [66–68] |
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| Huntington’s disease | HTT (CAG repeats) | (i) Increased vulnerability to cell stressors and BDNF withdrawal;
(ii) impaired lysosomal activity;
(iii) mitochondrial fragmentation;
(iv) alterations in transcription repressor activity;
(v) enhanced caspase 3/7 activity | Cortical neurons; GABAergic medium spiny neurons | (i) iPSCs with HTT mutation from homozygous and heterozygous HD patients
HD72-iPSC in the YAC128 model of HD | [5, 69–72] |
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| Neurodevelopmental disorders |
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| Familial Dysautonomia | IKBKAP | (i) Reduced IKAP protein level;
(ii) cell migration deficiency;
(iii) defects in neurogenic differentiation;
(iv) decreased in number of myelinated small fibers and intermediolateral column neurons | Sensory neurons; autonomic neurons | (i) FD iPSCs with mutation in IKBKAP gene | [73] |
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| Rett syndrome | MECP2e1, MECP2e2 | (i) Reduced soma size;
(ii) altered dendritic spine density;
(iii) dysfunction in action potential;
(iv) alterations in synaptic function;
(v) defects in synaptic plasticity | Glutamatergic neurons | (i) RS iPSCs with MECP2 mutation | [74, 75] |
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| ASD | NLGN1, NLGN3, SHANK2, SHANK3, NRXN1, NRXN3 | (i) Reduced glial differentiation;
(ii) altered gene expression related to cell adhesion and neuron differentiation;
(iii) deficits in neuronal specification, synapse formation and excitatory neurotransmission | Cortical neurons | (i) ASD iPSCs with functional knockdown of NRXN1 gene;
(ii) ASD iPSCs with SHANK3 deletion | [76, 77] |
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| Down syndrome | trisomy of chromosome 21 (HSA21) | (i) Alterations in neurogenesis and synaptogenesis;
(ii) elevated APP and Aβ42 expression;
(iii) Tau protein hyperphosphorylation;
(iv) poorly developed neural network;
(v) overproduction of reactive oxygen species | Neurons in the brain | (i) DS iPSCs with three pairs of chromosomes 21 (T21-iPSCs);
(ii) isogenic iPSCs from DS individuals;
(iii) DS iPSCs with trisomy 21 deletion through TKNEO;
(iv) DS iPSCs with trisomy 21 deletion through Xist | [70, 78–80] |
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| Schizophrenia | DISC1 | (i) Decreased neuronal connectivity;
(ii) synaptic deficits;
(iii) PSD95 downregulation;
(iv) fewer neurites | Neurons | (i) iPSCs from schizophrenia patients;
(ii) SZ iPSCs with a mutation in DISC1 gene | [81, 82] |
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